Tau is a cytoskeletal protein that is expressed mainly in neurons and is involved in several cellular processes, such as microtubule stabilization, axonal maintenance, and transport. Altered tau metabolism is related to different tauopathies being the most important Alzheimer’s disease where aberrant hyperphosphorylated and aggregated tau is found in the central nervous system. Here, we have analyzed that function in kidney by using tau knockout mice generated by integrating GFP-encoding cDNA into exon 1 of MAPT (here referred to as TauGFP/GFP). IVIS Lumina from PerkinElmer demonstrated GFP expression in the kidney. We then demonstrated by qPCR that the main tau isoform in the kidney is Tau4R. The GFP reporter allowed us to demonstrate that tau is found in the glomeruli of the renal cortex, and specifically in podocytes. This was further confirmed by immunohistochemistry. TauGFP/GFP mice present a podocyte cytoskeleton more dynamic as they contain higher levels of detyrosinated tubulin than wild-type mice. In addition, transmission electron microscopy studies demonstrated glomerular damage with a decrease in urinary creatinine. Our results prove that tau has an important role in kidney metabolism under normal physiological conditions.
Here we report a novel strategy to rejuvenate dentate gyrus cells in old mice. This approach involves the use of simple compounds such as folate and a peptide that binds to folate receptor α. The injection of folate or folate-mimicking peptide into the brain brought about a significant enhancement of cognition. Likewise, the dentate gyrus cells of these mice showed increased plasticity and DNA methylation levels. On the basis of our findings, we propose that folate, and folate-mimicking peptides acting on folate receptor α enhance neural plasticity in a similar fashion to the OSKM (Oct4, Sox2, Klf4, and Myc) Yamanaka factors. However, in marked contrast with the long-term cyclic treatment used for cell reprogramming with the latter, our method involves only a single injection of very simple small compounds. Our observations may facilitate future studies aimed at improving the clinical translation of cell reprogramming methods into the field of neurodegenerative disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.